Abstract

This study investigates two-phase growth patterns in early life and their associations with development of islet autoimmunity (IA) and type 1 diabetes (T1D). There were 7521 genetically high-risk children from Sweden, Finland, U.S. and Germany followed from birth for a median of 9.0 (IQR 5.7-10.6) years with available growth data. Of these, 761 children developed IA and 290 children progressed to T1D. Bayesian two-phase piecewise linear mixed models with a random change point were used to evaluate distinct growth phases in early life (Figure 1). Cox proportional hazard models were used to assess growth phase effects on risk of IA and progression to T1D. A higher rate of weight gain (kg/year) in the first phase was associated with an increased IA risk (HR =1.10, 95% CI 1.02, 1.18). A height growth pattern with a slower growth rate (cm/year) in the first phase, a higher growth rate in the second phase and younger age (months) at the phase transition was associated with an increased risk of progression from IA to T1D (HR=0.80, 95% CI 0.70, 0.91; HR=1.47, 95% CI 1.21, 1.78; HR=0.69, 95% CI 0.52, 0.93, respectively). A higher rate of weight gain in the second phase was associated with an increased risk of progression from IA to T1D (HR=2.54, 95% CI 1.36, 4.74) in children with first appearing GADA-only. Considering growth by phases in early life better clarified how specific growth phases contribute to the risk of IA and T1D. Disclosure X. Liu: None. K. Vehik: None. Y. Huang: None. H. Elding Larsson: None. J. Toppari: None. A. Ziegler: None. J. She: None. M. Rewers: None. W. Hagopian: Research Support; Self; Novo Nordisk A/S. B. Akolkar: None. J. Krischer: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases; National Institute of Allergy and Infectious Diseases; Eunice Kennedy Shriver National Institute of Child Health and Human Development; National Institute of Environmental Health Sciences; Centers for Disease Control and Prevention; JDRF; University of Florida (UL1TR000064); University of Colorado (UL1TR001082)

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